 |
Professor of Nephrology | Director of the Wellcome Centre for Cell-Matrix Research | Paediatric Nephrologist, University of Manchester, UKRachel graduated from Nottingham University Medical School in 1994. She completed clinical training in paediatric nephrology and began research training in 2004 with a Wellcome Research Training Fellowship to work in Peter Mathieson and Moin Saleem’s laboratory. She was appointed to an NIHR Academic Clinical Lectureship in 2007 and in 2008 began working in Martin Humphries’ group in Manchester. In 2010 she was awarded a Wellcome Intermediate Clinical Fellowship to establish her group; in 2016 she was awarded a Wellcome Senior Research Fellowship and this year she became Director of the Wellcome Centre for Cell-Matrix Research. Rachel’s research is focused on understanding mechanisms of basement membrane assembly and regulation and how these are affected in kidney disease such as Alport syndrome. Rachel combines her academic work with clinical duties as a Consultant Paediatric Nephrologist at the Royal Manchester Children’s Hospital. |
| Linking basement membrane biology to kidney human kidney disease Basement membranes are essential for tissue formation and function. Assembled as thin and dense scaffolds, basement membranes enwrap and support all organs and tissues. Although core components such as laminins and collagens are known, the full make up of basement membranes has been challenging to elucidate because of its biochemical insolubility and extracellular localization. Understanding basement membranes is important, as genetic defects in core basement membrane components cause a spectrum of rare human diseases such as Alport syndrome and large-scale genetic studies have shown that variants in these core genes are associated with more prevalent human diseases including diabetic kidney disease, haemorrhagic stroke and cardiovascular disease, which affect up to 1 in 3 of the population. By developing a robust new pipeline that combines immunolocalization, bioinformatics and genomic knock-in strategies, we recently curated 222 human genes that localise to basement membranes. Our studies also discovered new regulatory components, and identified loss of function variants in basement membrane elements that are associated with a wide spectrum of rare human disease within the 100,000 genomes project. I will describe this study during the talk and introduce the tools we have created to investigate basement membrane function. |
|